The <i>Drosophila melanogaster methuselah</i> Gene: A Novel Gene with Ancient Functions

<div><p>The <i>Drosophila melanogaster</i> G protein-coupled receptor gene, <i>methuselah</i> (<i>mth),</i> has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although <i>mth</i> belongs to a gene subfamily with 16 members in <i>D. melanogaster</i>, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that <i>mth</i> is an old gene. Under this hypothesis, in species distantly related to <i>D. melanogaster</i>, there should be a gene with features similar to those of <i>mth</i>. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the <i>D. virilis GJ12490</i> gene is the orthologous of <i>mth</i> in species distantly related to <i>D. melanogaster</i>. We also show that, in <i>D. americana</i> (a species of the <i>virilis</i> group of <i>Drosophila</i>), a common amino acid polymorphism at the <i>GJ12490</i> orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that <i>GJ12490</i> orthologous genes are candidates for developmental time and lifespan differences in <i>Drosophila</i> in general.</p>